Association between histone deacetylase activity and vitamin D-dependent gene expressions in relation to sulforaphane in human colorectal cancer cells.

Abstract

BACKGROUND:

It is relatively unknown as to how dietary bioactive compound sulforaphane (SFN) and vitamin D regulate gene expression in colorectal cancer. We hypothesized that a combination of SFN with vitamin D would prove beneficial in colorectal cancer. A combinatorial chemo-preventive strategy was employed to investigate the impact of SFN on chromatin remodeling in colorectal carcinoma. To understand the epigenetics-mediated changes in gene expression in response to SFN and vitamin D, Caco-2 cells were exposed for 24 h to vitamin D (100 nmol L-1 ) either alone or in combination with SFN and trichostatin A (20 and 1 μmol L-1 , respectively) at 70% confluency (proliferating) and after 13 days post-confluency (fully differentiated). Changes to VDR, CYP24A1, CYP27B1 and TRPV6 gene expressions were quantified using real-time PCR-based assays. Histone deacetylase (HDAC) inhibitor activity was assessed using HDAC I/II assay that measured global changes in acetylation status.

RESULTS:

In differentiated Caco-2 cells, none of the genes had significant changes from D alone group. D + SFN (P = 0.99) demonstrated an opposing effect from D alone and decreased VDR expression. However, in proliferating Caco-2 cells, D + SFN (P < 0.04) increased VDR expression and decreased CYP27B1 (P < 0.01) more than D alone (P = 0.38 and 0.07, respectively). Although statistically significant, D + SFN (P = 0.01) effect on HDAC inhibitor activity was less than trichostatin A alone group (P < 0.0004) or SFN alone group (P < 0.0014).

CONCLUSIONS:

The data suggest that colon cancer cells respond to dietary components differently under different conditions. The effect of vitamin D and SFN is selective and gene-specific in the complex multistep process of colorectal carcinogenesis in vitro. © 2020 Society of Chemical Industry.

• Authors: Sharmin Hossain, Zhenhua Liu, Richard J Wood
• Journal: Journal of the science of food and agriculture (J Sci Food Agric) Vol. 101 Issue 5 Pg. 1833-1843 (Mar 30 2021) ISSN: 1097-0010 [Electronic] England
• PMID: 32964464 (Publication Type: Journal Article)
• Copyright: © 2020 Society of Chemical Industry.

Chemical References

• Calcium Channels
• Hydroxamic Acids
• Isothiocyanates
• Receptors, Calcitriol
• Sulfoxides
• TRPV Cation Channels
• TRPV6 protein, human
• VDR protein, human
• Vitamin D
• trichostatin A
• CYP24A1 protein, human
• Vitamin D3 24-Hydroxylase
• Histone Deacetylases
• sulforaphane

Topics

• Acetylation (drug effects)
• Caco-2 Cells
• Calcium Channels (genetics, metabolism)
• Colonic Neoplasms (genetics, metabolism, prevention & control)
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylases (genetics, metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Isothiocyanates (pharmacology)
• Receptors, Calcitriol (genetics, metabolism)
• Sulfoxides (pharmacology)
• TRPV Cation Channels (genetics, metabolism)
• Vitamin D (pharmacology)
• Vitamin D3 24-Hydroxylase (genetics, metabolism)